Bicyclic aromatic compounds

ABSTRACT

The invention relates to novel bicyclic aromatic compounds which have the general formula (I):  
                 
 
     as well as to the use of these compounds in pharmaceutical compositions intended for use in human or veterinary medicine (dermatological, rheumatic, respiratory, cardiovascular and ophthalmological complaints in particular), or alternatively in cosmetic compositions.

[0001] The invention relates to bicyclic aromatic compounds as novel anduseful industrial products. It also relates to the use of these novelcompounds in pharmaceutical compositions intended for use in human orveterinary medicine, or alternatively in cosmetic compositions.

[0002] The compounds according to the invention have pronounced activityin the fields of cell differentiation and cell proliferation, and findapplications more particularly in the topical and systemic treatment ofdermatological complaints associated with a disorder of keratinization,dermatological (or other) complaints with an inflammatory and/orimmunoallergic component, and dermal or epidermal proliferations, thesebeing either benign or malignant. These compounds may also be used inthe treatment of degenerative diseases of connective tissue, forcombating both light-induced and chronological ageing of the skin andfor treating disorders of cicatrization. They moreover find anapplication in the ophthalmological field, in particular in thetreatment of corneopathies.

[0003] The compounds according to the invention may also be used incosmetic compositions for body and hair hygiene.

[0004] The compounds according to the invention may be represented bythe general formula (I) below:

[0005] in which:

[0006] R₁ represents

[0007] (i) the —CH₃ radical

[0008] (ii) the radical —CH₂OR₅

[0009] (iii) the radical —COR₆

[0010] R₅ and R₆ having the meaning given below

[0011] Ar represents a radical chosen from the radicals of formulae(a)-(e) below:

[0012] R₅ and R₇ having the meaning given below,

[0013] X represents

[0014] R₈ and R₉ having the meanings given below

[0015] R₂ and R₃, which may be identical or different, represent

[0016] (i) a hydrogen atom,

[0017] (ii) an alkyl radical having at least 3 carbon atoms, among whichthe carbon attached to the phenyl radical is substituted with at leasttwo carbon atoms,

[0018] (iii) a radical —OR₅,

[0019] (iv) a radical —SR₅,

[0020] R₅ having the meaning given below,

[0021] it being understood that R₂ and R₃, taken together, may form withthe adjacent aromatic ring a 5- or 6-membered ring optionallysubstituted with methyl groups and/or optionally interrupted by anoxygen or sulphur atom,

[0022] and it being understood that R₂ and R₃ cannot at the same timehave the meanings (i), (iii) and (iv) mentioned above,

[0023] R₄ and R₇, which may be identical or different, represent ahydrogen atom, a halogen atom, a linear or branched alkyl radical havingfrom 1 to 20 carbon atoms or a radical —OR₅,

[0024] R₅ represents a hydrogen atom, a lower alkyl radical or a radical—OCR₁₀

[0025] R₁₀ having the meaning given below,

[0026] R₆ represents:

[0027] (a) a hydrogen atom

[0028] (b) a lower alkyl radical

[0029] (c) a radical of formula:

[0030] R′ and R″ having the meaning given below,

[0031] (d) a radical —OR₁₁

[0032] R₁₁ having the meaning given below,

[0033] R₈ and R₉, which may be identical or different, represent ahydrogen atom or a lower alkyl radical,

[0034] R₁₀ represents a lower alkyl radical,

[0035] R₁₁ represents a hydrogen atom, a linear or branched alkylradical having from 1 to 20 carbon atoms, an alkenyl radical, a mono- orpolyhydroxyalkyl radical, an optionally substituted aryl or aralkylradical, a sugar residue or an amino acid or peptide residue,

[0036] R′ and R″, which may be identical or different, represent ahydrogen atom, a lower alkyl radical, a mono- or polyhydroxyalkylradical, an optionally substituted aryl radical or an amino acid orsugar residue, or alternatively, taken together form a heterocycle.

[0037] The invention is also directed towards the salts of the compoundsof formula (I) when R₁ represents a carboxylic acid function and thegeometrical and optical isomers of the said compounds of formula (I).

[0038] When the compounds according to the invention are in the form ofsalts, they are preferably salts of an alkali metal or alkaline-earthmetal, or alternatively of zinc or of an organic amine.

[0039] According to the present invention, the term lower alkyl radicalis understood to refer to a radical having from 1 to 12, preferably from1 to 9, carbon atoms, advantageously the methyl, ethyl, propyl,isopropyl, butyl, tert-butyl, pentyl, hexyl, heptyl, nonyl, decyl anddodecyl radicals.

[0040] The expression linear alkyl radical having from 1 to 20 carbonatoms is understood to refer in particular to the methyl, ethyl, propyl,pentyl, hexyl, octyl, decyl, dodecyl, hexadecyl and octadecyl radicals.

[0041] The expression branched alkyl radical having from 1 to 20 carbonatoms is understood to refer in particular to the 2-ethylhexyl,2-methylbutyl, 2-methylpentyl, 1-methylhexyl and 3-methylheptylradicals.

[0042] Among the alkyl radicals having at least 3 carbon atoms, wherethe carbon attached to the phenyl radical is substituted with at leasttwo carbon atoms, mention may be made of the tert-butyl, isopropyl,1,1-dimethylhexyl and 1,1-dimethyldecyl radical. Preferably, theseradicals have not more than 20 carbon atoms, even more preferably notmore than 12 carbon atoms. Advantageously, the radical (ii) is thetert-butyl radical.

[0043] Among the monohydroxyalkyl radicals, a radical having 2 or 3carbon atoms, in particular a 2-hydroxyethyl, 2-hydroxypropyl or3-hydroxypropyl radical, is preferred.

[0044] Among the polyhydroxyalkyl radicals, a radical having from 3 to 6carbon atoms and from 2 to 5 hydroxyl groups, such as the2,3-dihydroxypropyl, 2,3,4-trihydroxybutyl or 2,3,4,5-tetrahydroxypentylradicals or the pentaerythritol residue, is preferred.

[0045] Among the aryl radicals, a phenyl radical optionally substitutedwith at least one halogen atom, a hydroxyl or a nitro function ispreferred.

[0046] Among the aralkyl radicals, the benzyl or phenethyl radicaloptionally substituted with at least one halogen atom, a hydroxyl or anitro function is preferred.

[0047] Among the alkenyl radicals, a radical containing from 2 to 5carbon atoms and having one or more ethylenic unsaturations, moreparticularly such as the allyl radical, is preferred.

[0048] The term sugar residue is understood to refer to a residuederived in particular from glucose, galactose or mannose, oralternatively from glucuronic acid.

[0049] The term amino acid residue is understood to refer in particularto a residue derived from lysine, from glycine or from aspartic acid,and the term peptide residue is understood to refer more particularly toa dipeptide or tripeptide residue resulting from the combination ofamino acids.

[0050] Lastly, the term heterocycle is understood to refer preferably toa piperidino, morpholino, pyrrolidino or piperazino radical optionallysubstituted in position 4 with a C₁-C₆ alkyl or a mono- orpolyhydroxyalkyl radical as defined above.

[0051] When the radicals R₄ and R₇ represent a halogen atom, this ispreferably a fluorine, bromine or chlorine atom.

[0052] Among the compounds of formula (I) above which fall within thescope of the present invention, mention may be made in particular of thefollowing:

[0053] 5-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-acrylic acid,

[0054] 5-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-propiolic acid,

[0055] 2-(3-tert-Butyl-4-methoxyohenyl)-4-thiophene-acrylic acid,

[0056] 4-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-acrylic acid,

[0057]5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneacrylicacid,

[0058]4-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneacrylicacid,

[0059]4-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-thiopheneacrylicacid,

[0060]5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiophenepropiolicacid,

[0061]3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylpropiolicacid,

[0062]N-Methyl-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-pyrroleacrylicacid,

[0063]3-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylic acid,

[0064]N-Methyl-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylicacid,

[0065]4-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylicacid,

[0066]3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,

[0067]3-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylpropiolicacid,

[0068]2-Methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,

[0069]2-Propyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,

[0070]2-Heptyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,

[0071]2-Methoxymethoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,

[0072]2-Hydroxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,

[0073]3-(3-Methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid,

[0074]3-(3-Propyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid,

[0075]3-(3-Heptyloxy-5,6,7,8-tetrahydo-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid,

[0076]3-(3-Methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid,

[0077]3-(3-Hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid,

[0078] 3-(4,4,7-Trimethylthiochroman-6-yl)-phenylacrylic acid,

[0079]N-Ethyl-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylamide,

[0080]N-(4-Hydroxyphenyl)-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylamide,

[0081]3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid morpholide,

[0082] Ethyl3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylate,

[0083]3-[3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]but-2-enoicacid,

[0084]4-Methoxymethoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,

[0085]4-Hydroxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,

[0086]4-Methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,

[0087]4-Propyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,

[0088]4-Heptyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,

[0089]3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]acrolein,

[0090]3-[3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]prop-2-en-1-ol,

[0091]cis-3-[3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]but-2-enoicacid,

[0092]cis-3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,

[0093]5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-3-pyridineacrylicacid,

[0094]3-(3-Butyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid,

[0095]6-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyridineacrylicacid.

[0096] According to the present invention, the compounds of formula (I)more particularly preferred are those for which at least one, andpreferably all, of the following conditions are satisfied:

[0097] R₁ represents the radical —COR₆

[0098] Ar represents the radicals of formula (a) or (d)

[0099] X represents the radical

[0100] R₂ and R₃, taken together, form, with the adjacent aromatic ring,a 5- or 6-membered ring optionally substituted with methyl groups and/oroptionally interrupted by an oxygen or sulphur atom.

[0101] The subject of the present invention is also processes for thepreparation of the compounds of formula (I), in particular according tothe reaction scheme given in FIG. 1.

[0102] Thus, the derivatives of formula (Ia) may be obtained (FIG. 1)from aldehyde or ketone derivatives (5) according to a Horner-typereaction with a lithium or sodium derivative of a phosphonate (7). Thecarbonyl compounds (5) may be obtained:

[0103] either by a coupling reaction between a boronic acid (3) and ahalo derivative (4). This reaction is carried out in the presence of apalladium catalyst, for example tetrakis(triphenylphosphine)-palladiumaccording to the conditions described by N. Miyaura et al., SyntheticCommunications (1981) 11(7), 513-519. The boronic acid derivative (3)may be obtained, for example, from the halo derivative (1) by conversioninto the lithium reagent (2), followed by reaction with trimethyl borateand hydrolysis.

[0104] or by a coupling reaction between a zinc derivative (8) and ahalogenated ester derivative (9) in the presence of a catalyst, forexample a palladium or a nickel derivative (NiCl₂ dppe), followed byconversion of the ester function (10) into alcohol (11) and oxidation toaldehyde (5).

[0105] The compounds of formula (Ib) may be obtained (FIG. 1) from theacetylenic derivative (6) by reaction with n-butyllithium and thencarboxylation in the presence of CO₂. The acetylenic compounds (6) maybe obtained either:

[0106] from aldehyde derivatives (5) (when R₈ is a hydrogen atom), byreaction with carbon tetrabromide and triphenylphosphine in-order togive a 2′,2′-dibromostyrene derivative which is converted intoacetylenic derivative by a non-nucleophilic base such as n-butyllithium,in an aprotic solvent such as tetrahydrofuran.

[0107] from ketone derivatives (5) (when R₈ is a lower alkyl) by areaction sequence comprising treatment with a base such as lithiumdiisopropylamide and then with a dialkyl phosphate chloride and againwith lithium diisopropylamide.

[0108] When R₃ represents the radical —COOH, the compounds are preparedby protecting R₁ with a protecting group of alkyl, allylic, benzylic ortert-butyl type.

[0109] The passage to the free form may be carried out:

[0110] in the case of an alkyl protecting group, using sodium hydroxideor lithium hydroxide in an alcoholic solvent such as methanol, or inTHF.

[0111] in the case of an allylic protecting group, using a catalyst suchas certain transition metal complexes in the presence of a secondaryamine such as morpholine.

[0112] in the case of a benzylic protecting group, by debenzylation inthe presence of hydrogen using a catalyst such as palladium-on-charcoal.

[0113] in the case of a protecting group of tert-butyl type, usingtrimethylsilyl iodide.

[0114] The subject of the present invention is also, as medicinalproduct, the compounds of formula (I) as defined above.

[0115] Some of these compounds are active in a test which consists inidentifying molecules that are RXR agonists, as described in Frenchpatent application No. 95/07301 filed on Jun. 19, 1995 by the Applicant.This test comprises the following steps: (i) a sufficient amount of acompound which is an active ligand of at least one receptor of thesteroidal/thyroidal receptor superfamily, other than a ligand which isspecific for the RXR receptors, and which can heterodimerize with RXRs,such as an RAR-agonist molecule, is applied topically to part of theskin of a mammal, (ii) a molecule capable of exhibiting RXR-agonistactivity is administered systemically or topically to this same part ofthe mammal's skin, before, during or after step (i), and (iii) theresponse on that part of the mammal's skin thus treated is evaluated.Thus, the response to a topical application, to a mammal's ear, of anRAR-agonist molecule, which corresponds to an increase in the thicknessof this ear, may be increased by the systemic or topical administrationof an RXR-agonist molecule. Some of the compounds according to theinvention are also active in the test of differentiation of mouseembryonic teratocarcinoma cells (F9) (Cancer Research 43, pp. 5268,1983) and/or in the test of inhibition of ornithine decarboxylase afterinduction with TPA in mice (Cancer Research 38, pp. 793-801, 1978).These tests show the activities of these compounds in the fields of celldifferentiation and cell proliferation respectively.

[0116] The compounds according to the invention are particularlysuitable in the following fields of treatment:

[0117] 1) For treating dermatological complaints associated with akeratinization disorder which has a bearing on differentiation and onproliferation, in particular for treating common acne, comedones,polymorphonuclear leukocytes, rosacea, nodulocystic acne, acneconglobata, senile acne and secondary acnes such as solar,medication-related or profession-related acne.

[0118] 2) For treating other types of keratinization disorder, inparticular ichthyosis, ichthyosiform states, Darier's disease,palmoplantar keratoderma, leucoplasias and leucoplasiform states, andcutaneous or mucous (buccal) lichen.

[0119] 3) For treating other dermatological complaints associated with akeratinization disorder with an inflammatory and/or immunoallergiccomponent and, in particular, all forms of psoriasis, whether it iscutaneous, mucous or ungual psoriasis and even psoriatic rheumatism, oralternatively cutaneous atopy, such as eczema or respiratory atopy oralternatively gingival hypertrophy; the compounds may also be used forsome inflammatory complaints which show no keratinization disorder,

[0120] 4) For treating all dermal or epidermal hyperproliferations,whether benign or malignant and whether they are of viral origin orotherwise, such as common warts, flat warts and verruciformepidermodysplasia, it being possible for the oral or floridpapillomatoses and the hyperproliferations to be induced by ultravioletradiation, in particular in the case of basocellular and spinocellularepitheliloma,

[0121] 5) For treating other dermatological disorders such as bullosisand collagen diseases,

[0122] 6) For treating certain ophthalmological disorders, in particularcorneopathies,

[0123] 7) For repairing or combating ageing of the skin, whether this islight-induced or chronological ageing, or for reducing actinic keratosesand pigmentations, or any pathologies associated with chronological oractinic ageing,

[0124] 8) For preventing or curing the stigmata of epidermal and/ordermal atrophy induced by local or systemic corticosteroids, or anyother form of cutaneous atrophy,

[0125] 9) For preventing or treating cicatrization disorders or forpreventing or repairing vibices,

[0126] 10) For combating disorders of sebaceous functioning such as thehyperseborrhoea of acne or simple seborrhoea,

[0127] 11) In the treatment or prevention of cancerous or precancerousstates,

[0128] 12) In the treatment of inflammatory complaints such asarthritis,

[0129] 13) In the treatment of any general or skin complaint of viralorigin,

[0130] 14) In the prevention or treatment of alopecia,

[0131] 15) In the treatment of dermatological or general complaintshaving an immunological component,

[0132] 16) In the treatment of complaints of the cardiovascular systemsuch as arteriosclerosis or hypertension, as well as insulin-independentdiabetes,

[0133] 17) In the treatment of skin disorders caused by exposure to UVradiation.

[0134] In the therapeutic fields mentioned above, the compoundsaccording to the invention may advantageously be employed in combinationwith other compounds having retinoid-type activity, with D vitamins orderivatives thereof, with corticosteroids, with anti-free-radicalagents, α-hydroxy or α-keto acids or derivatives thereof, oralternatively with ion-channel blockers. The expression D vitamins orderivatives thereof is understood to refer, for example, to vitamin D₂or D₃ derivatives and in particular 1,25-dihydroxy vitamin D₃. Theexpression anti-free-radical agent is understood to refer, for example,to α-tocopherol, superoxide dismutase, ubiquinol or certainmetal-chelating agents. The expression α-hydroxy or α-keto acids orderivatives thereof is understood to refer, for example, to lactic acid,malic acid, citric acid, glycolic acid, mandelic acid, tartaric acid,glyceric acid or ascorbic acid or salts, amides or esters thereof.Lastly, the expression ion-channel blockers is understood to refer, forexample, to Minoxidil (2,4-diamino-6-piperdinopyrimidine 3-oxide) andderivatives thereof.

[0135] The subject of the present invention is also medicinalcompositions containing at least one compound of formula (I) as definedabove, one of the optical or geometric isomers thereof or one of thesalts thereof.

[0136] The subject of the present invention is thus a novel medicinalcomposition intended in particular for treating the abovementionedcomplaints, and which is characterized in that it comprises, in apharmaceutically acceptable support which is compatible with the mode ofadministration selected for this composition, at least one compound offormula (I), one of the optical or geometric isomers thereof or one ofthe salts thereof.

[0137] The compounds according to the invention may be administeredenterally, parentarally, topically or ocularly.

[0138] Via the enteral route, the medicinal products may be in the formof tablets, gelatin capsules, sugar-coated tablets, syrups, suspensions,solutions, powders, granules, emulsions, microspheres or nanospheres orpolymeric or lipid vesicles which allow controlled release. Via theparenteral route, the compositions may be in the form of solutions orsuspensions for infusion or for injection.

[0139] The compounds according to the invention are generallyadministered at a daily dose of about 0.01 mg/kg to 100 mg/kg of bodyweight, taken in 1 to 3 doses.

[0140] Via the topical route, the pharmaceutical compositions based oncompounds according to the invention are more particularly intended fortreating the skin and mucous membranes and may, in this case, be in theform of ointments, creams, milks, salves, powders, impregnated pads,solutions, gels, sprays, lotions or suspensions. They may also be in theform of microspheres or nanospheres or polymeric or lipid vesicles orpolymeric patches and hydrogels which allow controlled release. Thesetopical-route compositions may moreover be either in anhydrous form orin an aqueous form, depending on the clinical indication.

[0141] Via the ocular route, they are mainly eyedrops.

[0142] The compositions for topical or ocular use contain at least onecompound of formula (I) defined above, or one of the optical orgeometric isomers thereof, or alternatively one of the salts thereof, ata concentration preferably of between 0.001% and 5% by weight relativeto the total weight of the composition.

[0143] The compounds of formula (I) according to the invention also findan application in the cosmetic field, in particular in body and hairhygiene and especially for treating skin-types with a tendency towardsacne, for promoting the regrowth of the hair, for combating hair loss,for controlling the greasy appearance of the skin or the hair, inprotection against the harmful effects of sunlight or in the treatmentof physiologically dry skin-types, and for preventing and/or combatinglight-induced or chronological ageing.

[0144] In the cosmetic field, the compounds according to the inventionmay also advantageously be employed in combination with other compoundshaving retinoid-type activity, with D vitamins or derivatives thereof,with corticosteroids, with anti-free-radical agents, α-hydroxy or α-ketoacids or derivatives thereof, or alternatively with ion-channelblockers, all of these different products being as defined above.

[0145] The present invention is this also directed towards a cosmeticcomposition which is characterized in that it comprises, in acosmetically acceptable support which is suitable for topicalapplication, at least one compound of formula (I) as defined above, orone of the optical or geometric isomers thereof or one of the saltsthereof, it being possible in particular for this cosmetic compositionto be in the form of a cream, a milk, a lotion, a gel, microspheres ornanospheres or polymeric or lipid vesicles, a soap or a shampoo.

[0146] The concentration of compound of formula (I) in the cosmeticcompositions according to the invention is advantageously between 0.001%and 3% by weight relative to the composition as a whole.

[0147] The medicinal and cosmetic compositions according to theinvention may also contain inert additives or even pharmacodynamicallyor cosmetically active additives or combinations of these additives and,in particular, wetting agents; depigmenting agents such as hydroquinone,azelaic acid, caffeic acid or kojic acid; emollients; moisturizingagents such as glycerol, PEG 400, thiamorpholinone and derivativesthereof, or urea; anti-seborrhoea or anti-acne agents such asS-carboxymethylcysteine, S-benzylcysteamine, the salts and thederivatives thereof, or benzoyl peroxide; antibiotics such aserythromycin and esters thereof, neomycin, clindamycin and estersthereof, and tetracyclines; antifungal agents such as ketoconazole or4,5-polymethylene-3-isothiazolidones; agents for promoting the regrowthof the hair, such as minoxidil (2,4-diamino-6-piperidinopyrimidine3-oxide) and derivatives thereof, diazoxide(7-chloro-3-methyl-1,2,4-benzothiadiazine 1,1-dioxide) and phenytoin(5,4-diphenylimidazolidine-2,4-dione); non-steroidal anti-inflammatoryagents; carotenoids and, in particular, b-carotene; anti-psoriaticagents such as anthraline and derivatives thereof and, lastly,eicosa-5,8,11,14-tetraynoic acid and eicosa-5,8,11-triynoic acid, theesters and the amides thereof.

[0148] The compositions according to the invention may also containflavour-enhancing agents, preserving agents such as para-hydroxybenzoicacid esters, stabilizing agents, moisture regulators, pH regulators,osmotic pressure modifiers, emulsifying agents, UV-A and UV-B screeningagents, and antioxidants such as α-tocopherol, butylhydroxyanisole orbutylhydroxytoluene.

[0149] Several examples of the production of active compounds of formula(I) according to the invention, as well as various solid formulationsbased on such compounds, will now be given by way of illustration andwith no limitation. In the preceding description and the followingexamples, percentages are given by weight unless otherwise stated.

EXAMPLE 1 5- (3-tert-Butyl-4-methoxyphenyl)-2-thiophene-acrylic acid

[0150] (a) Methyl5-(3-tert-butyl-4-methoxyphenyl)-2-thiophenecarboxylate

[0151] A solution of 2 g (8.2 mmol) of3-tert-butyl-4-methoxybromobenzene is added dropwise to a suspension of300 mg (12 mmol) of magnesium in 10 ml of THF. Once the addition iscomplete, the mixture is refluxed for one hour. At room temperature,1.35 g (9.9 mmol) of anhydrous zinc chloride are added and the mixtureis stirred for one hour. 1.2 g (5.5 mmol) of methyl5-bromo-2-thiophenecarboxylate and 60 mg (0.12 mmol) of the NiCl₂/DPPEcomplex are then added successively and the mixture is left stirring atroom temperature for 12 hours. The reaction medium is poured intoice-water and extracted with ethyl ether and the organic phase isseparated out after settling has taken place, dried over magnesiumsulphate and evaporated. The residue obtained is chromatographed on acolumn of silica eluted with a mixture of hexane and dichloromethane(50/50% by volume). After evaporation of the solvents, 1.56 g (93%) ofthe expected methyl ester are collected, with a melting point of 94-5°C.

[0152] (b) 5-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-methanol

[0153] 1.5 g (5 mmol) of the above methyl ester and 50 ml of anhydrousTHF are introduced into a three-necked flask under a stream of nitrogen.280 mg (7.4 mmol) of lithium aluminium hydride are added and the mixtureis refluxed for four hours. It is hydrolyzed with potassium sodiumtartrate solution, the salt is filtered off and the filtrate isevaporated. The residue obtained is purified by chromatography on acolumn of silica eluted with a mixture of dichloromethane and hexane(70/30% by volume). After evaporation of the solvents, 1.26 g (92%) ofthe expected alcohol are recovered, in the form of a colourless oil.

[0154] (c) 5-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-carboxaldehyde

[0155] 7.15 g (19 mmol) of pyridinium dichromate and 350 ml ofdichloromethane are introduced into a round-bottomed flask. A solutionof 3.9 g (14 mmol) of5-(3-tert-butyl-4-methoxyphenyl)-2-thiophenemethanol in 50 ml ofdichloromethane is added dropwise, at 0° C., and the mixture is stirredat room temperature for two hours. The reaction medium is filteredthrough silica and, after evaporation, 3.26 g (84%) of the expectedaldehyde are recovered, in the form of a brown oil.

[0156] (d) Ethyl 5-(3-tert-butyl-4-methoxyphenyl)-2-thiopheneacrylate

[0157] 200 mg (6.6 mmol) of sodium hydride (80% in oil) and 50 ml ofdimethoxyethane are introduced into a three-necked flask under a streamof nitrogen and a solution of 1.3 ml (6.6 mmol) of triethylphosphoacetate in 10 ml of dimethoxyethane is added dropwise. Themixture is stirred at room temperature for one hour and then, at 0° C.,a solution of 1.5 g (5.5 mmol) of5-(3-tert-butyl-4-methoxyphenyl)-2-thiophenecarboxaldehyde in 20 ml ofdimethoxyethane is added dropwise. The reaction medium is stirred atroom temperature for four hours and is then poured into water andextracted with ethyl ether, and the organic phase is separated out aftersettling has taken place, dried over magnesium sulphate and evaporated.The residue obtained is purified by chromatography on a column of silicaeluted with a mixture of dichloromethane and hexane (30/70% by volume);1.88 g (100%) of the expected ethyl ester are collected, in the form ofa brown oil.

[0158] (e) 5-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-acrylic acid

[0159] 1.88 g (5.4 mmol) of the above ethyl ester, 20 ml of methanol and1.88 g (47 mmol) of sodium hydroxide ae introduced into a round-bottomedflask and the mixture is refluxed for four hours. The reaction medium isevaporated to dryness, the residue is taken up in water and acidified topH 1, and the solid is filtered off and dried. The solid obtained isrecrystallized from ethanol, filtered off and dried. 1.09 g (63%) of5-(3-tert-butyl-4-methoxyphenyl)-2-thiopheneacrylic acid are collected,with a melting point of 218-9° C.

EXAMPLE 2 5-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-propiolic acid

[0160] (a)2′,2′-Dibromo-5-(3-tert-butyl-4-methoxyphenyl)-2-thiopheneethylene

[0161] 1.79 g (6.5 mmol) of5-(3-tert-butyl-4-methoxyphenyl)-2-thiophenecarboxaldehyde prepared inExample 1 (c) and 50 ml of dichloromethane are introduced into around-bottomed flask. 4.32 g (13 mmol) of carbon tetrabromide, 3.41 g(13 mmol) of triphenylphosphine and 850 mg (13 mmol) of zinc powder aresuccessively added and the mixture is stirred at room temperature fortwo hours. The reaction medium is evaporated and the residue obtained ispurified by chromatography on a column of silica eluted withdichloromethane. 2.5 g (89%) of the expected product are collected.

[0162] (b) S-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-acetylene

[0163] 2.48 g (5.7 mmol) of2′,2′-dibromo-5-(3-tert-butyl-4-methoxyphenyl)-2-thiopheneethylene and40 ml of THF are introduced into a three-necked flask under a stream ofnitrogen. 5.1 ml (12.7 mmol) of n-butyllithium solution (2.5 M inhexane) are added dropwise, at −78° C., and the mixture is allowed toreturn to room temperature over one hour. The reaction medium is pouredinto water and extracted with ethyl ether, and the organic phase isseparated out after settling has taken place, dried over magnesiumsulphate and evaporated. The residue obtained is purified bychromatography on a column of silica eluted with heptane. 1.1 g (71%) ofthe expected acetylenic derivative are collected, in the form of ayellow oil.

[0164] (c) 5-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-propiolic acid

[0165] 1.1 g (4 mmol) of the above acetylenic derivative and 20 ml ofTHF are introduced into a three-necked flask under a stream of nitrogen.1.95 ml (4.9 mmol) of n-butyllithium (2.5 M in hexane) are addeddropwise, at −78° C., and the mixture is stirred for thirty minutes. Astream of CO₂ is passed through at −78° C., for fifteen minutes and themixture is allowed to return to room temperature. The reaction medium ispoured into aqueous ammonium chloride solution and extracted with ethylether, and the organic phase is separated out after settling has takenplace, dried over magnesium sulphate and evaporated. The residueobtained is purified by chromatography on a column of silica eluted withdichloromethane. After evaporation of the solvents, 300 mg (23%) of5-(3-tert-butyl-4-methoxyphenyl)-2-thiophenepropiolic acid arecollected, with a melting point of 124-6° C.

EXAMPLE 3 2-(3-tert-Butyl-4-methoxyphenyl)-4-thiophene-acrylic acid

[0166] (a) 3-tert-Butyl-4-methoxyphenylboronic acid

[0167] 4 g (16.5 mmol) of 3-tert-butyl-4-methoxy-bromobenzene and 50 mlof THF are introduced into a three-necked flask under a stream ofnitrogen. 7.9 ml (19.8 mmol) of n-butyllithium (2.5 M in hexane) areadded dropwise at −78° C., the mixture is stirred for 15 minutes at thistemperature, 5.6 ml (49.5 mmol) of trimethyl borate are added and themixture is stirred for 2 hours. 20 ml of hydrochloric acid (1 N) areadded at −50° C. and the mixture is allowed to return to roomtemperature. The reaction medium is extracted with ethyl ether and theorganic phase is separated out after settling has taken place, driedover magnesium sulphate and evaporated. 3.79 g (100%) of the expectedboronic acid are collected, which is used in its present state for therest of the synthesis.

[0168] (b) Ethyl 2-(3-tert-butyl-4-methoxyphenyl)-4-thiophenecarboxylate

[0169] 260 mg (0.5 mol) of tetrakis(triphenyl-phosphine)palladium(O), 50ml of toluene and 2.59 g (10.9 mmol) of ethyl2-bromo-4-thiophenecarboxylate are introduced into a three-necked flaskunder a stream of nitrogen and the mixture is stirred at roomtemperature for 20 minutes. 3.7 g (16.5 mmol) of3-tert-butyl-4-methoxyphenylboronic acid and 11 ml of aqueous sodiumcarbonate solution (2 N) are then added and the mixture is refluxed for8 hours. The reaction medium is evaporated to dryness, the residue istaken up in water and ethyl ether and the organic phase is separated outafter settling has taken place, dried over magnesium sulphate andevaporated. The residue is purified by chromatography on a column ofsilica eluted with a mixture of ethyl acetate and heptane (10/90% byvolume). 3.53 g (69%) of ethyl2-(3-tert-butyl-4-methoxyphenyl)-4-thiophenecarboxylate are obtained.

[0170] (c) 2-(3-tert-Butyl-4-methoxyphenyl)-4-thiophene-methanol

[0171] In a similar manner to Example 1(b), starting with 3.5 g (11mmol) of ethyl 2-(3-tert-butyl-4-methoxyphenyl)-4-thiophenecarboxylate,3.2 g (100%) of the expected alcohol are obtained in the form of a brownoil.

[0172] (d) 2-(3-tert-Butyl-4-methoxyphenyl)-4-thiophene-carboxaldehyde

[0173] In a similar manner to Example 1(c), starting with 3.2 g (11mmol) of the above alcohol, 2.3 g (76%) of2-(3-tert-butyl-4-methoxyphenyl)-4-thiophene-carboxaldehyde are obtainedin the form of a brown oil.

[0174] (e) Ethyl 2-(3-tert-butyl-4-methoxyphenyl)-4-thiophene-acrylate

[0175] In a similar manner to Example 1(d), by reaction of 1.3 g (4.7mmol) of 2-(3-tert-butyl-4-methoxyphenyl)-4-thiophenecarboxaldehyde with1.28 g (5.7 mmol) of triethyl phosphonoacetate, 1.1 g (67%) of theexpected ethyl ester are obtained, with a melting point of 119-20° C.

[0176] (f) 2-(3-tert-Butyl-4-methoxyphenyl)-4-thiophene-acrylic acid

[0177] In a similar manner to Example 1(e), starting with 1.1 g (3.2mmol) of the above ethyl ester, 750 mg (74%)2-(3-tert-butyl-4-methoxyphenyl)-4-thiophene-acrylic acid are obtained,with a melting point of 197-8° C.

EXAMPLE 4 4-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-acrylic acid

[0178] (a) 4-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-carboxaldehyde

[0179] In a similar manner to Example 3(b), by reaction of 2.68 g (12.3mmol) of 3-tert-butyl-4-methoxyphenylboronic acid with 1.55 g (2.12mmol) of 4-bromo-2-thiophenecarboxaldehyde, 2.13 g (95%) of4-(3-tert-butyl-4-methoxyphenyl)-2-thiophene-carboxaldehyde are obtainedin the form of a yellow oil.

[0180] (b) Ethyl 4-(3-tert-butyl-4-methoxyohenyl)-2-thiopheneacrylate

[0181] In a similar manner to Example 1(d), by reaction of 1.2 g (4.3mmol) of 4-(3-tert-butyl-4-methoxyphenyl)-2-thiophenecarboxaldehyde with1.17 g (5.2 mmol) of triethyl phosphonoacetate, 1.55 g (100%) of theexpected ethyl ester are obtained in the form of an oil.

[0182] (c) 4-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-acrylic acid

[0183] In a similar manner to Example 1(e), starting with 1.55 g (4.5mmol) of the above ethyl ester, 1.14 g (88%) of4-(3-tert-butyl-4-methoxyphenyl)-2-thiophene-acrylic acid are obtained,with a melting point of 206-7° C.

EXAMPLE 55-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneacrylicacid

[0184] (a) 3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthylboronicacid,

[0185] In a similar manner to Example 3(a), starting with 5 g (178 mmol)of 3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-bromonaphthalene, 4.22 g(100%) of boronic acid are obtained.

[0186] (b)5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiophenecarboxaldehyde

[0187] In a similar manner to Example 3(b), by reaction of 4.2 g (17mmol) of 3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylboronic acidwith 2.17 g (11.3 mmol) of 5-bromo-2-thiophenecarboxaldehyde, 2.1 g(60%) of the expected aldehyde are obtained, with a melting point of130-5° C.

[0188] (c) Ethyl5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneacrylate

[0189] In a similar manner to Example 1(d), by reaction of 2 g (6.4mmol) of5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiophene-carboxaldehydewith 1.73 g (7.7 mmol) of triethyl phosphonoacetate, 2.02 g (82%) of theexpected ethyl ester are obtained.

[0190] (e)5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneacrylicacid

[0191] In a similar manner to Example 1(e), starting with 2 g (5.2 mmol)of the above ethyl ester, 1.79 g (96%) of5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneacrylicacid are obtained, with a melting point of 175-7° C.

EXAMPLE 64-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneacrylicacid

[0192] (a)4-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiophenecarboxaldehyde

[0193] In a similar manner to Example 3(b), by reaction of 4.2 g (17mmol) of 3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylboronic acidwith 2.17 g (11.3 mmol) of 4-bromo-2-thiophenecarboxaldehyde, 2.75 g(78%) of the expected aldehyde are obtained, with a melting point of144-6° C.

[0194] (b) Ethyl4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneacrylate

[0195] In a similar manner to Example 1(d), by reaction of 2.7 g (8.6mmol) of4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiophene-carboxaldehydewith 2.1 ml (10.4 mmol) of triethyl phosphonoacetate, 2.76 g (84%) ofthe expected ethyl ester are obtained.

[0196] (c)4-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneacrylicacid

[0197] In a similar manner to Example 1(e), starting with 2.7 g (7.1mmol) of the above ethyl ester, 2.5 g (98%) of4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneacrylicacid are obtained, with a melting point of 215-20° C.

EXAMPLE 74-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-thiopheneacrylicacid

[0198] (a) 5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthylboronic acid

[0199] In a similar manner to Example 3(a), starting with 5 g (18.7mmol) of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-bromonaphthalene, 4.3g (100%) of the expected boronic acid are obtained.

[0200] (b)4-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-thiophenecarboxaldehyde

[0201] In a similar manner to Example 3(b), by reaction of 4.3 g (18.7mmol) of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylboronic acidwith 2.36 g (12.3 mmol) of 4-bromo-2-thiophenecarboxaldehyde, 2.3 g(63%) of the expected aldehyde derivative are obtained, with a meltingpoint of 84-5° C.

[0202] (c) Ethyl4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-thiopheneacrylate

[0203] In a similar manner to Example 1(d), by reaction of 2.28 g (8.3mmol) of(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-thiophene-carboxaldehydewith 2 ml (9.9 mmol) of triethyl phosphonoacetate, 810 mg (26%) of theexpected ethyl ester are obtained, with a melting point of 82-4° C.

[0204] (d)4-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-thiopheneacrylicacid

[0205] In a similar manner to Example 1(e), starting with 810 mg (2.2mmol) of the above ethyl ester, 720 mg (96%) of4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-thiopheneacrylicacid are obtained, with a melting point of 182-5° C.

EXAMPLE 85-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiophenepropiolicacid

[0206] (a)2′,2′-Dibromo-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneethylene

[0207] In a similar manner to Example 2(a), starting with 3 g (9.6 mmol)of5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiophene-carboxaldehyde,4.56 g (100%) of2′,2′-dibromo-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneethyleneare obtained.

[0208] (b)5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneacetylene

[0209] In a similar manner to Example 2(b), starting with 4.5 g (9.6mmol)2′,2′-dibromo-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneethylene,1.42 g (48%) of5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiophene-acetyleneare obtained.

[0210] (c)5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiophenepropiolicacid

[0211] In a similar manner to Example 2(c), starting with 1.4 g (4.5mmol) of the above acetylenic derivative, 800 mg (51%) of5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiophenepropiolicacid are obtained, with a melting point of 138-40° C.

EXAMPLE 93-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylpropiolicacid

[0212] (a) 3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthylboronicacid,

[0213] 100 g (0.356 mol) of2-bromo-3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalene and 1liter of THF are introduced into a two-liter reactor under a stream ofnitrogen, and the solution is cooled to −60° C. 157 ml (0.392 mol) ofn-butyllithium (2.5 M in hexane) are added dropwise and the mixture isstirred for one hour. 121 ml (1.07 mol) of trimethyl borate are addeddropwise at −70° C. and the mixture is stirred for one hour. 500 ml ofhydrochloric acid (1 N) are added at −35° C. and the mixture is allowedto return to room temperature. The reaction medium is extracted withethyl acetate and the organic phase is separated out after settling hastaken place, washed twice with 500 ml of hydrochloric acid (1 N), driedover magnesium sulphate and evaporated. 83 g (95%) of the expectedboronic acid are collected.

[0214] (b)3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehyde

[0215] 700 ml of DME, 2.4 g (2 mmol) oftetrakistriphenylphosphinepalladium(O) and 8.44 g (45.6 mmol) of3-bromobenzaldehyde are introduced into a three-necked flask under astream of nitrogen and the mixture is stirred for 10 minutes. A solutionof 17 g (69.1 mmol) of3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylboronic acid in 25 mlof ethanol are then added, followed by 46 ml (91 mmol) of potassiumcarbonate solution (2 M) and the mixture is refluxed for four hours. Thereaction medium is cooled and filtered and the solid is washed withbicarbonate solution and then with ethyl acetate. The solid obtained isrecrystallized from ethanol and 7 g (50%) of the expected aldehyde arecollected, with a melting point of 104-5° C.

[0216] (c)2′,2′-Dibromo-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylethylene

[0217] In a similar manner to Example 2(a), starting with 2 g (6.5 mmol)of the above aldehyde, 1.96 g (65%) of the expected product are obtainedin the form of a colourless oil.

[0218] (d)3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacetylene

[0219] In a similar manner to Example 2(b), starting with 1.96 g (4.23mmol) of2′,2′-dibromo-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylethylene,1.29 g (99%) of the expected acetylenic derivative are obtained in theform of a pale yellow oil.

[0220] (e)3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylpropiolicacid

[0221] In a similar manner to Example 2(c), starting with 1.17 g (3.9mmol) of the above acetylenic derivative, 900 mg (67%) of3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylpropiolicacid are obtained, with a melting point of 180-1° C.

EXAMPLE 10N-Methyl-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-pyrroleacrylicacid

[0222] (a)4-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-pyrrolecarboxaldehyde

[0223] In a similar manner to Example 3(b), by reaction of 5.9 g (25.6mmol) of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylboronic acidwith 3.7 g (21.3 mmol) of 4-bromo-2-pyrrolecarboxaldehyde, 1.3 g (21.6%)of the expected product are obtained, with a melting point of 211-2° C.

[0224] (b)N-Methyl-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-pyrrolecarboxaldehyde

[0225] 1.3 g (4.6 mmol) of4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-pyrrolecarboxaldehydeand 50 ml of THF are introduced into a three-necked flask under a streamof nitrogen. 300 mg (10 mmol) of sodium hydride (80% in oil) are addedportionwise and the mixture is stirred until the evolution of gas hasceased. 640 μl (10 mmol) of iodomethane are then added and the mixtureis stirred at room temperature for one hour. The reaction medium ispoured into water and extracted with ethyl acetate, and the organicphase is separated out after settling has taken place, dried overmagnesium sulphate and evaporated. The residue obtained is purified bychromatography on a column of silica eluted with a mixture ofdichloromethane and heptane (70/30). After evaporation of the solvents,600 mg (44%) of the expected product are collected.

[0226] (c) EthylN-methyl-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-pyrroleacrylate

[0227] In a similar manner to Example 1(d), by reaction of 480 mg (1.3mmol) ofN-methyl-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-pyrrolecarboxaldehydewith 400 μl (152 mmol) of triethyl phosphonoacetate, 350 mg of theexpected ethyl ester are obtained in the form of an oil.

[0228] (d)N-Methyl-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-pyrroleacrylic acid

[0229] In a similar manner to Example 1(e), starting with 350 mg (0.94mmol) of the above ethyl ester, 170 mg (23%) ofN-methyl-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-pyrroleacrylicacid are obtained, with a melting point of 185-6° C.

EXAMPLE 113-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylic acid

[0230] (a)3-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylcarboxaldehyde

[0231] In a similar manner to Example 3(b), by reaction of 6.43 g (27.7mmol) of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylboronic acidwith 2.7 ml (23.1 mmol) of 4-bromobenzaldehyde, 2.05 g (24%) of3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-phenylcarboxaldehydeare obtained in the form of a pale yellow oil.

[0232] (b) Ethyl3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylate

[0233] In a similar manner to Example 1(d), by reaction of 800 mg (2.7mmol) of3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylcarboxaldehydewith 650 ml (3.3 mmol) of triethyl phosphonoacetate, 900 mg (91%) of theexpected ethyl ester are obtained in the form of a colourless oil.

[0234] (c)3-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylic acid

[0235] In a similar manner to Example 1e), starting with 1.22 g (2.7mmol) of the above ethyl ester, 380 mg (41%) of3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylic acidare obtained, with a melting point of 210-1° C.

EXAMPLE 12N-Methyl-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylicacid

[0236] (a) N-Methyl-4-bromo-2-pyrrolecarboxaldehyde

[0237] In a similar manner to Example 10(b), by reaction of 4 g (23mmol) of 4-bromo-2-pyrrolecarboxaldehyde with 1.7 ml (27.6 mmol) ofiodomethane, 2.3 g (50%) of the expected product are obtained, with amelting point of 123-4° C.

[0238] (b)N-Methyl-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrrolecarboxaldehyde

[0239] In a similar manner to Example 3(b), by reaction of 3 g (12.1mmol) of 3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylboronic acidwith 1.9 g (10.1 mmol) of N-methyl-4-bromo-2-pyrrole-carboxaldehyde,1.85 g (59%) of the expected product are obtained in the form of a paleyellow oil.

[0240] (c) EthylN-methyl-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylate

[0241] In a similar manner to Example 1(d), by reaction of 1.85 g (6mmol) ofN-methyl-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrrole-carboxaldehydewith 1.4 ml (7.2 mmol) of triethyl phosphonoacetate, 2.1 g (92%) of theexpected ethyl ester are obtained in the form of an orange-coloured oil.

[0242] (d)N-Methyl-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylicacid

[0243] In a similar manner to Example 1(e), starting with 2 g (5.3 mmol)of the above ethyl ester, 730 mg (39.5%) ofN-methyl-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylicacid are obtained, with a melting point or 185-6° C.

EXAMPLE 134-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylicacid

[0244] (a)4-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrrolecarboxaldehyde

[0245] In a similar manner to Example 3(b), by reaction of 2.47 g (10mmol) of 3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylboronic acidwith 1.5 g (8.4 mmol) of 4-bromo-2-pyrrolecarboxaldehyde, 950 mg (38.5%)of the expected aldehyde are obtained, with a melting point of 128-9° C.

[0246] (b) Ethyl4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylate

[0247] In a similar manner to Example 1(d), by reaction of 500 mg (1.7mmol) of4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrrolecarboxaldehydewith 400 μl (2 mmol) of triethyl phosphonoacetate, 570 mg (92%) of theexpected ethyl ester are obtained.

[0248] (c)4-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylicacid

[0249] In a similar manner to Example 1(e), starting with 570 mg (1.9mmol) of ethyl4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylate,240 mg (37%) of4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylicacid are obtained, with a melting point of 245-6° C.

EXAMPLE 143-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid

[0250] In a similar manner to Example 9(b), by reaction of 73.4 g (0.30mol) of 3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylboronic acidwith 44.7 g (0.20 mol) of 4-bromophenylacrylic acid, and afterrecrystallization from ethanol, 48 g (61%) of3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid are obtained, with a melting point of 207-8° C.

EXAMPLE 153-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylpropiolicacid

[0251] (a)2′,2′-Dibromo-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylethylene

[0252] In a similar manner to Example 2(a), starting with 2.05 g (7mmol) of3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)benzaldehyde[prepared in Example 11(a)], 1.07 g (35%) of the expected product areobtained in the form of an oil.

[0253] (b)3-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylpropiolicacid.

[0254] 900 mg (2 mmol) of2′,2′-dibromo-3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthyl)phenylethyleneand 40 ml of THF are introduced into a three-necked flask under a streamof nitrogen. 2.2 ml (5.2 mmol) of n-butyllithium solution (2.5 M inhexane) are added dropwise at −50° C. and the mixture is allowed toreturn to room temperature. CO₂ is introduced at 0° C. for 20 minutesand the mixture is stirred at room temperature for one hour. Thereaction medium is poured into saturated ammonium chloride solution andadjusted to pH 1 with hydrochloric acid, the mixture is extracted withethyl acetate and the organic phase is separated out after settling hastaken place, dried over magnesium sulphate and evaporated. The residueobtained is purified by chromatography on a column of silica eluted witha mixture of dichloromethane and methanol (95/5). After evaporation ofthe solvents, 80 mg (12%) of3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylpropiolicacid are collected, with a melting point of 164-5° C.

EXAMPLE 162-Methoxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid

[0255] (a)2-Hydroxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehyde.

[0256] In a similar manner to Example 9(b), by reaction of 15 g (51mmol) of 3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylboronic acidwith 8.16 g (41 mmol) of 5-bromo-2-hydroxybenzaldehyde, 11.7 g (89%) of2-hydroxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehydeare obtained, with a melting point of 138-9° C.

[0257] (b)2-Methoxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehyde.

[0258] In a similar manner to Example 10(b), by reaction of 2 g (6.2mmol) of2-hydroxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehydewith 425 μl (6.8 mmol) of iodomethane, 1.68 g (88%) of the expectedproduct are obtained.

[0259] (c) Ethyl2-methoxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylate.

[0260] In a similar manner to Example 1(d), by reaction of 1.65 g (5mmol) of2-methoxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehydewith 1.68 g (7.5 mmol) of triethyl phosphonoacetate, 1.7 g (83%) of theexpected ethyl ester are obtained in the form of an oil.

[0261] (d)2-Methoxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid.

[0262] In a similar manner to Example 1(e), starting with 1.6 g (3.9mmol) of the above ethyl ester, 1.4 g (93%) of2-methoxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid are obtained, with a melting point of 181-2° C.

EXAMPLE 172-Propyloxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid.

[0263] (a)2-Propyloxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehyde.

[0264] In a similar manner to Example 10(b), by reaction of 2 g (6.2mmol) of2-hydroxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehyde[prepared in Example 16(a)] with 670 μl (6.8 mmol) of 1-iodopropane, 2.2g (88%) of the expected product are obtained in the form of a colourlessoil.

[0265] (b) Ethyl2-propyloxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylate.

[0266] In a similar manner to Example 1(d), by reaction of 2.18 g (6mmol) of2-propyloxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehydewith 2.03 g (9 mmol) of triethyl phosphonoacetate, 2.13 g (82%) of theexpected ethyl ester are obtained in the form form of a yellow oil.

[0267] (c)2-Propyloxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid.

[0268] In a similar manner to Example 1(e), starting with 2.1 g (4.8mmol) of the above ethyl ester, 1.68 g (86%) of2-propyloxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid are obtained, with a melting point of 125-6° C.

EXAMPLE 182-Heptyloxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid.

[0269] (a)2-Heptyloxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehyde.

[0270] In a similar manner to Example 10(b), by reaction of 2 g (9.3mmol) of2-hydroxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehyde[prepared in Example 16(a)] with 1.1 ml (6.8 mmol) of 1-bromoheptane,1.88 g (72%) of the expected product are obtained in the form of ayellow oil.

[0271] (b) Ethyl2-heptyloxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylate.

[0272] In a similar manner to Example 1(d), by reaction of 1.78 g,(4.2mmol) of2-heptyloxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehydewith 1.44 g (6.3 mol) of triethyl phosphonoacetate, 1.89 g (90%) of theexpected ethyl ester are obtained in the form of a yellow oil.

[0273] (c)2-Heptyloxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid.

[0274] In a similar manner to Example 1(e), starting with 1.89 g (3.9mmol) of the above ethyl ester, 1.2 g (67%) of2-heptyloxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid are obtained, with a melting point of 137-8° C.

EXAMPLE 192-Methoxymethoxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylic

[0275] (a)2-Methoxymethoxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehyde

[0276] In a similar manner to Example 10(b), by reaction of 3 g (9.3mmol) of2-hydroxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehyde[prepared in Example 16(a)] with 777 μl (10.2 mmol) of methoxymethylchloride, 3.5 g (100%) of the expected product are obtained in the formof an oil.

[0277] (b) Ethyl2-methoxymethoxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylate.

[0278] In a similar manner to Example 1(d), by reaction of 3.4 g (9.3mmol) of2-methoxymethoxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-benzaldehydewith 4.16 g (18.6 mmol) of triethyl phosphonoacetate, 3.5g (86%) of theexpected ethyl ester are obtained, with a melting point of 100-1° C.

[0279] (c)2-Methoxymethoxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid.

[0280] In a similar manner to Example 1(e), starting with 1.5 g (3.4mmol) of the above ethyl ester, 1.2 g (86%) of2-methoxymethoxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid are obtained, with a melting point of 191-2° C.

EXAMPLE 202-Hydroxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid.

[0281] (a) Methyl2-hydroxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylate

[0282] 1.9 g (4.35 mmol) of2-methoxymethoxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid, 20 ml of methanol and 30 ml of THF are introduced into around-bottomed flask. 2.8 ml of concentrated sulphuric acid are addedand the mixture is stirred at room temperature for 12 hours. Thereaction medium is poured into water and extracted with ethyl ether, andthe organic phase is separated out after settling has taken place,washed with water, dried over magnesium sulphate and evaporated. 1.63 g(95%) of methyl2-hydroxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylateare collected.

[0283] (b)2-Hydroxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid.

[0284] In a similar manner to Example 1(e), starting with 1.63 g (4.25mmol) of the above ethyl ester, 1.3 g (85%) of2-hydroxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid are obtained, with a melting point of 204-5° C.

EXAMPLE 213-(3-Methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid.

[0285] (a)3-Bromo-2-methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene.

[0286] 7 g (24.7 mmol) of3-bromo-2-hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene and40 ml of DMF are introduced into a three-necked flask under a stream ofnitrogren. 890 mg (29.6 mmol) of sodium hydride (80% in oil) are addedportionwise and the mixture is stirred until the evolution of gas hasceased. 1.7 ml (27 mmol) of iodomethane are then added and the mixtureis stirred at room temperature for one hour. The reaction medium ispoured into water and extracted with ethyl ether, and the organic phaseis separated out after settling has taken place, dried over magnesiumsulphate and evaporated. 7.3 g (99%) of the expected product arecollected in the form of an oil which crystallizes slowly. Melting point77-8° C.

[0287] (b)2-Methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-naphthylboronic acid.

[0288] In a similar manner to Example 3 (a), starting with 6.7 g (22.5mmol) of3-bromo-2-methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene,4.54 g (77%) of the expected boronic acid are obtained, with a meltingpoint of 151-2° C.

[0289] (c)3-(3-Methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid.

[0290] In a similar manner to Example 9(b), by reaction of 2.62 g (10mmol) of 2-methoxy-5,6,7,8-tetramethylnaphthylboronic acid with 1.51 g(6.7 mmol) of 3-bromophenylacrylic acid, 1.1 g (45%) of3-(3-methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid are obtained, with a melting point of 187-8° C.

EXAMPLE 223-(3-Propyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid.

[0291] (a)3-Bromo-2-propyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene.

[0292] In a similar manner to Example 21(a), by reaction of 7 g (24.7mmol) of3-bromo-2-hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene with2.45 ml (27 mmol) of 1-bromopropane, 8.1 g (100%) of3-bromo-2-propyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthaleneare obtained in the form of an orange-coloured oil.

[0293] (b)2-Propyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthylboronic acid.

[0294] In a similar manner to Example 3(a), by reaction of 8 g (24.6mmol) of3-bromo-2-propyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene,5.7 g (80%) of the expected boronic acid are obtained, with a meltingpoint of 138-9° C.

[0295] (c)3-(3-Propyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid.

[0296] In a similar manner to Example 9(b), by reaction of 5 g (17.2mmol) of2-propyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthylboronic acidwith 2.6 g (11.5 mmol) of 3-broophenylacrylic acid, 1.66 g (35%) of3-(3-propyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid are obtained, with a melting point of 172-3° C.

EXAMPLE 233-(3-Heptyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid.

[0297] (a)3-Bromo-2-heptyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene.

[0298] In a similar manner to Example 21(a), by reaction of 7 g (24.7mmol) of3-bromo-2-hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene with4.24 ml (27 mmol) of 1-bromoheptane, 10 g (100%) of3-bromo-2-heptyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthaleneare obtained in the form of a brown oil.

[0299] (b)2-Heptyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthylboronic acid.

[0300] In a similar manner to Example 3(a), starting with 10 g (26.2mmol) of3-bromo-2-heptyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene,6.1 g (67%) of the expected boronic acid are obtained, with a meltingpoint of 102-3° C.

[0301] (c)3-(3-Heptyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid.

[0302] In a similar manner to Example 9(b), by reaction of 5 g (14.4mmol) of2-heptyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthylboronic acidwith 2.52 g (11.1 mmol) of 3-bromophenylacrylic acid, 2.7 g (54%) of3-(3-heptyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid are obtained, with a melting point of 112-3° C.

EXAMPLE 243-(3-Methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid.

[0303] (a)3-Bromo-2-methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene.

[0304] In a similar manner to Example 21(a), by reaction of 7 g (24.7mmol) of3-bromo-2-hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene with2.05 ml (27 mmol) of methoxymethyl chloride, 8.1 g (100%) of3-bromo-2-methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthaleneare obtained in the form of a light-brown oil.

[0305] (b)2-Methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthylboronicacid.

[0306] In a similar manner to Example 3(a), starting with 8 g (24.4mmol) of3-bromo-2-methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene,5.5 g (77%) of the expected boronic acid are obtained, with a meltingpoint of 133-4° C.

[0307] (c)3-(3-Methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid.

[0308] In a similar manner to Example 9(b), by reaction of 5.3 g (18.1mmol) of2-methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthylboronicacid with 3.16 g (14 mmol) of 3-bromophenylacrylic acid, 4.39 g (80%) of3-(3-methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid are obtained, with a melting point of 156-7° C.

EXAMPLE 253-(3-Hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid.

[0309] (a) Methyl3-(3-hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylate.

[0310] 2 g (5 mmol) of3-(3-methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid, 10 ml of methanol and 10 ml of THF are introduced into around-bottomed flask. 2.8 ml of concentrated sulphuric acid are addedand the mixture is stirred at room temperature for &é hours. Thereaction medium is poured into water and extracted with ethyl ether, andthe organic phase is separated out after settling has taken place,washed with water, dried over magnesium sulphate and evaporated. 1.80 g(98%) of the expected methyl ester are collected, with a melting pointof 182-3° C.

[0311] (b)3-(3-Hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid.

[0312] In a similar manner to Example 1(e), starting with 1.5 g (4.1mmol) of the above methyl ester, 1.3 g (90%) of3-(3-hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid are obtained, with a melting point of 244-5° C.

EXAMPLE 26 3-(4,4,7-Trimethylthiochroman-6-yl)phenylacrylic acid.

[0313] (a) 1-Methyl-3-(3-methylbut-2-enyl)sulphanylbenzene.

[0314] 5 g (40 mmol) of 3-methylthiophenol, 5.6 g (40 mmol) of potassiumcarbonate and 50 ml of DMF are introduced into a three-necked flask. 7.2g (48 mmol) of 3-methyl-2-butene bromide are added and the mixture isstirred at room temperature for four hours. The reaction medium ispoured into water and extracted with ethyl ether, and the organic phaseis separated out after settling has taken place, dried over magnesiumsulphate and evaporated. 7.8 g (100%) of the expected product arecollected in the form of a yellow oil.

[0315] (b) 4,4,7-Trimethylthiochroman.

[0316] 7 g (36.4 mmol) of1-methyl-3-(3-methylbut-2-enyl)sulphanylbenzene and 50 ml of toluene areintroduced into a round-bottomed flask and 10.4 g (54.6 mmol) ofpara-toluenesulphonic acid are added. The mixture is refluxed for fourhours. The reaction medium is evaporated to dryness, the residue istaken up in water and ethyl ether and the organic phase is separated outafter settling has taken place, dried over magnesium sulphate andevaporated. 6.8 g (97%) of the thiochroman are collected in the form ofa brown oil.

[0317] (c) 6-Bromo-4,4,7-trimethylthiochroman.

[0318] 6.2 g (32.2 mmol) of 4,4,7-trimethylthiochroman, 40 ml ofdichloromethane and 90 mg of iron powder are introduced into athree-necked flask. 1.65 ml (32.2 mmol) of bromine are added and themixture is stirred at room temperature for two hours. The reactionmedium is poured into sodium bicarbonate solution and extracted withdichloromethane, and the organic phase is separated out after settlinghas taken place, dried over magnesium sulphate and evaporated. Theresidue obtained is purified by chromatography on a column of silicaeluted with heptane. 5.9 g (67%) of the bromo derivative are collectedin the form of a pale yellow oil.

[0319] (d) 4,4,7-Trimethylthiochromanylboronic acid.

[0320] In a similar manner to Example 3(a), starting with 5.8 g (21.4mmol) of 6-bromo-4,4,7-trimethylthiochroman, 3.88 g (76%) of theexpected boronic acid are obtained, with a melting point of 252-3° C.

[0321] (e) 3-(4,4,7-Trimethylthiochroman-6-yl)phenylacrylic acid.

[0322] In a similar manner to Example 9(b), by reaction of 1.5 g (6.3mmol) of 4,4,7-trimethylthiochromanylboronic acid with 1.2 g (5.3 mmol)of 3-bromophenylacrylic acid, 1.1 g (99%) of3-(4,4,7-trimethylthiochroman-6-yl)phenylacrylic acid are obtained, witha melting point of 102-3° C.

EXAMPLE 27N-Ethyl-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylamide.

[0323] (a)3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacryloylchloride.

[0324] 3.5 g (10 mmol) of3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid and 50 ml of dichloromethane are introduced into a round-bottomedflask and 2 ml (10 mmol) of dicylcohexylamine are added. The mixture isstirred at room temperature for 10 minutes and 729 μl (10 mmol) ofthionyl chloride are then introduced with stirring for 15 minutes. Thereaction medium is evaporated to dryness, the residue is taken up inethyl ether, the dicyclohexylamine salt is filtered off and the filtrateis evaporated. 3.7 g (100%) of the crude acid chloride are collected,which will be used in its current state for the rest of the synthesis.

[0325] (b)N-Ethyl-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylamide.

[0326] 20 ml of THF are introduced into a round-bottomed flask and 2.8ml (35 mmol) of ethylamine solution (70%) are added. A solution of 1.2 g(3.2 mmol) of3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacryloylchloride in 40 ml of THF is added dropwise and the mixture is stirred atroom temperature for one hour. The reaction medium is acidified withhydrochloric acid and extracted with ethyl ether, and the organic phaseis separated out after settling has taken place, dried over magnesiumsulphate and evaporated. The residue obtained is purified bychromatography on a column of silica eluted with dichloromethane. Afterevaporation of the solvents, 817 mg (68%) ofN-ethyl-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylamideare collected, with a melting point of 158-9° C.

EXAMPLE 28N-(4-Hydroxyphenyl)-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylamide.

[0327] In a similar manner to Example 27(a), by reaction of 1.2 g (3.2mmol) of3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacryloylchloride with 349 mg (3.2 mmol) of 4-hydroxyaniline, 810 mg of (57%) ofN-(4-hydroxyphenyl)-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylamideare obtained, with a melting point of 240-1° C.

EXAMPLE 29 3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro2-naphthyl)phenylacrylic acid morpholide.

[0328] In a similar manner to Example 27(a), by reaction of 1.3 g (3.4mmol) of3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacryloylchloride with 620 μl of (7.12 mmol) of morpholine, 1.25 g (88%) of3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid morpholide are obtained, with a melting point of 158-9° C.

EXAMPLE 30 Ethyl3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylate.

[0329] In a similar manner to Example 1(d), by reaction of 5 g (16.3mmol) of3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)benzaldehyde with4.79 g (21.2 mmol) of triethyl phosphonoacetate, 5 g (81%) of ethyl3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylateare obtained, with a melting point of 70-2° C.

EXAMPLE 313-[3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]but-2-enoicacid.

[0330] (a)3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)acetophenone.

[0331] In a similar manner to Example 9(b), by reaction of 5 g (20.3mmol) of 3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthylboronic acidwith 2.7 g (13.5 mmol) of 3-bromoacetophenone, 4.3 g (90%) of theexpected product are obtained, with a melting point of 89-90° C.

[0332] (b) Ethyl3-[3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]but-2-enoate.

[0333] In a similar manner to Example 1(d), by reaction of 3.7 g (11.5mmol) of3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)acetophenone with3.9 g (17.3 mmol) of triethyl phosphonoacetate, 2.67 g (60%) of theexpected ethyl ester are obtained in the form of a yellow oil.

[0334] (c)3-[3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]but-2-enoicacid.

[0335] In a similar manner to Example 1(e), starting with 2.5 g (6.4mmol) of the above ethyl ester, 1.63 g (70%) of3-[3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]but-2-enoicacid are obtained, with a melting point of 166-7° C.

EXAMPLE 32

[0336] Various solid formulations based on compounds according to theinvention are illustrated in this example. ORAL ROUTE (a) 0.2 g tabletCompound of Example 1 0.001 g Starch 0.114 g Dicalcium phosphate 0.020 gSilica 0.020 g Lactose 0.030 g Talc 0.010 g Magnesium stearate 0.005 g(b) Drinkable suspension in 5 ml ampoules Compound of Example 3 0.001 gGlycerol 0.500 g 70% Sorbitol 0.500 g Sodium saccharinate 0.010 g Methylpara-hydroxybenzoate 0.040 g Flavouring qs Purified water qs 5 ml (c)0.8 g tablet Compound of Example 5 0.500 g Pregelatinized starch 0.100 gMicrocrystalline cellulose 0.115 g Lactose 0.075 g Magnesium stearate0.010 g (d) Drinkable suspension in 10 ml ampoules Compound of Example 20.050 g Glycerol 1.000 g 70% Sorbitol 1.000 g Sodium saccharinate 0.010g Methyl para-hydroxybenzoate 0.080 g Flavouring qs Purified water qs 10ml TOPICAL ROUTE (a) Ointment Compound of Example 21 0.020 g Isopropylmyristate 81.700 g Liquid petroleum jelly 9.100 g Silica (“Aerosil 200”sold by 9.180 g Degussa) (b) Ointment Compound of Example 9 0.300 gWhite petroleum jelly codex qs 100 g (c) Nonionic water-in-oil creamCompound of Example 7 0.100 g Mixture of emulsifying lanolin 39.900 galcohols, waxes and oils (“Anhydrous Eucerin” sold by BDF) Methylpara-hydroxybenzoate 0.075 g Propyl para-hydroxybenzoate 0.075 g Steriledemineralized water qs 100 g (d) Lotion Compound of Example 30 0.100 gPolyethylene glycol (PEG 400) 69.900 g 95% Ethanol 30.000 g (e)Hydrophobic ointment Compound of Example 25 0.300 g Isopropyl myristate36.400 g Silicone oil (“Rhodorsil 47 V 300” 36.400 g sold byRhône-Poulenc) Beeswax 13.600 g Silicone (“Abil 300,000 cst” 100 g soldby Goldschmidt) qs (f) Nonionic oil-in-water cream Compound of Example14 0.500 g Cetyl alcohol 4.000 g Glyceryl monostearate 2.500 g PEG 50stearate 2.500 g Karite butter 9.200 g Propylene glycol 2.000 g Methylpara-hydroxybenzoate 0.075 g Propyl para-hydroxybenzoate 0.075 g Steriledemineralized water qs 100 g

1. Bicyclic aromatic compounds, characterized in that they correspond tothe general formula (I) below:

in which: —R₁ represents (i) the —CH₃ radical (ii) the radical —CH₂OR₅(iii) the radical —COR₆ R₅ and R₆ having the meaning given below Arrepresents a radical chosen from the radicals of formulae (a)-(e) below:

R₅ and R₇ having the meaning given below, X represents

R₈ and R₉ having the meanings given below R₂ and R₃, which may beidentical or different, represent (i) a hydrogen atom, (ii) an alkylradical having at least 3 carbon atoms, among which the carbon attachedto the phenyl radical is substituted with at least two carbon atoms,(iii) a radical —OR₅, (iv) a radical —SR₅, R₅ having the meaning givenbelow, it being understood that R₂ and R₃, taken together, may form withthe adjacent aromatic ring a 5- or 6-membered ring optionallysubstituted with methyl groups and/or optionally interrupted by anoxygen or sulphur atom, and it being understood that R₂ and R₃ cannot atthe same time have the meanings (i), (iii) and (iv) mentioned above, R₄and R₇, which may be identical or different, represent a hydrogen atom,a halogen atom, a linear or branched alkyl radical having from 1 to 20carbon atoms or a radical —OR₅, R₅ represents a hydrogen atom, a loweralkyl radical or a radical —COR₁₀ R₁₀ having the meaning given below, R₆represents: (a) a hydrogen atom (b) a lower alkyl radical (c) a radicalof formula:

R′ and R″ having the meaning given below, (d) a radical —OR₁₁ R₁₁ havingthe meaning given below, R₈ and R₉, which may be identical or different,represent a hydrogen atom or a lower alkyl radical, R₁₀ represents alower alkyl radical, R₁₁ represents a hydrogen atom, a linear orbranched alkyl radical having from 1 to 20 carbon atoms, an alkenylradical, a mono- or polyhydroxyalkyl radical, an optionally substitutedaryl or aralkyl radical, a sugar residue or an amino acid or peptideresidue, R′ and R″, which may be identical or different, represent ahydrogen atom, a lower alkyl radical, a mono- or polyhydroxyalkylradical, an optionally substituted aryl radical or an amino acid orsugar residue, or alternatively, taken together form a heterocycle, aswell as the salts thereof and the optical and geometrical isomersthereof.
 2. Compounds according to claim 1, characterized in that theyare in the form of salts of an alkali metal or alkaline-earth metal, oralternatively of zinc or of an organic amine.
 3. Compounds according toclaim 1, characterized in that they are taken, alone or as mixtures,from the group consisting of:5-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-acrylic acid,5-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-propiolic acid,2-(3-tert-Butyl-4-methoxyphenyl)-4-thiophene-acrylic acid,4-(3-tert-Butyl-4-methoxyphenyl)-2-thiophene-acrylic acid,5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiopheneacrylicacid,4-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiophenepropiolicacid,4-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-thiopheneacrylicacid,5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-thiophenepropiolicacid,3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylpropiolicacid,N-Methyl-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-pyrroleacrylicacid, 3-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid,N-Methyl-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylicacid,4-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyrroleacrylicacid,3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,3-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylpropiolicacid,2-Methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,2-Propyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,2-Heptyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,2-Methoxymethoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,2-Hydroxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,3-(3-Methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid,3-(3-Propyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid,3-(3-Heptyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid,3-(3-Methoxymethoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid,3-(3-Hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid, 3-(4,4,7-Trimethylthiochroman-6-yl)phenylacrylic acid,N-Ethyl-3-(3,5,5,8,8-pentamethyl-5,6,7,tetrahydro-2-naphthyl)phenylacrylamide,N-(4-Hydroxyphenyl)-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylamide,3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid morpholide, Ethyl3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylate,3-[3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]but-2-enoicacid,4-Methoxymethoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,4-Hydroxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,4-Methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,4-Propyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,4-Heptyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]acrolein,3-[3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]prop-2-en-1-ol,cis-3-[3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenyl]but-2-enoicacid,cis-3-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)phenylacrylicacid,5-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-3-pyridineacrylicacid,3-(3-Butyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)phenylacrylicacid,6-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-2-pyridineacrylicacid.
 4. Compounds according to claim 1, characterized in that they haveat least one, and preferably all, of the following characteristics: R₁represents the radical —COR₅ Ar represents the radicals of formula (a)or (d) X represents the radical

R₂ and R₃, taken together, form, with the adjacent aromatic ring, a 5-or 6-membered ring optionally substituted with methyl groups and/oroptionally interrupted by an oxygen or sulphur atom.
 5. Compoundsaccording to any one of the preceding claims, for use as a medicinalproduct.
 6. Compounds according to claim 5, for use as a medicinalproduct intended for the treatment of dermatological complaintsassociated with a keratinization disorder which has a bearing ondifferentiation and on proliferation, in particular for treating commonacne, comedones, polymorphonuclear leukocytes, rosacea, nodulocysticacne, acne conglobata, senile acne and secondary acnes such as solar,medication-related or profession-related acne; for treating other typesof keratinization disorder, in particular ichthyosis, ichthyosiformstates, Darier's disease, palmoplantar keratoderma, leucoplasias andleucoplasiform states, and cutaneous or mucous (buccal) lichen; fortreating other dermatological complaints associated with akeratinization disorder with an inflammatory and/or immunoallergiccomponent and, in particular, all forms of psoriasis, whether it iscutaneous, mucous or ungual psoriasis and even psoriatic rheumatism, oralternatively cutaneous atopy, such as eczema or respiratory atopy oralternatively gingival hypertrophy; the compounds may also be used forsome inflammatory complaints which show no keratinization disorder; fortreating all dermal or epidermal hyperproliferations, whether benign ormalignant and whether they are of viral origin or otherwise, such ascommon warts, flat warts and verruciform epidermodysplasia, it beingpossible for the oral or florid papillomatoses and thehyperproliferations to be induced by ultraviolet radiation, inparticular in the case of basocellular and spinocellular epithelioma;for treating other dermatological disorders such as bullosis andcollagen diseases; for treating certain ophthalmological disorders, inparticular corneopathies; for repairing or combating ageing of the skin,whether this is light-induced or chronological ageing, or for reducingactinic keratoses and pigmentations, or any pathologies associated withchronological or actinic ageing; for preventing or curing the stigmataof epidermal and/or dermal atrophy induced by local or systemiccorticosteroids, or any other form of cutaneous atrophy; for preventingor treating cicatrization disorders or for preventing or repairingvibices; for favouring cicatrization, for combating disorders ofsebaceous functioning such as the hyperseborrhoea of acne or simpleseborrhoea; in the treatment or prevention of cancerous or precancerousstates, more particularly promyelocytary leukemia; in the treatment ofinflammatory complaints such as arthritis; in the treatment of anygeneral or skin complaint of viral origin; in the prevention ortreatment of alopecia; in the treatment of dermatological complaintshaving an immunological component; in the treatment of complaints of thecardiovascular system such as arteriosclerosis or hypertension, as wellas insulin-independent diabetes, in the treatment of skin disorderscaused by exposure to UV radiation.
 7. Pharmaceutical composition,characterized in that it comprises, in a pharmaceutically acceptablesupport, at least one of the compounds as defined in any of claims 1 to4.
 8. Composition according to claim 7, characterized in that theconcentration of compound(s) according to one of claims 1 to 4 isbetween 0.001% and 5% by weight relative to the composition as a whole.9. Cosmetic composition, characterized in that it comprises, in acosmetically acceptable support, at least one of the compounds asdefined in any one of claims 1 to
 4. 10. Composition according to claim9, characterized in that the concentration of compound(s) according toone of claims 1 to 4 is between 0.001% and 3% by weight relative to thecomposition as a whole.
 11. Use of a cosmetic composition as defined ineither of claims 9 and 10, for body or hair hygiene.